Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Male germ cells-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse progenitor spermatogonia by DNA repair defects and sustained endoplasmic reticulum stress [ Ribo-Seq]

ABSTRACT: Eukaryotic translation initiation factor 5 (eIF5) promotes protein translation by regulating the ternary complex (TC) of eIF2•GTP•Met-tRNAi. A previous study showed that eIF5 is closely associated with testicular germ cell tumors (TGCTs). However, the role of eIF5 in mouse spermatogenesis remains unclear. Our study found that eIF5 is highly expressed in the cytoplasm of germ cells compared to other cells in the mouse testis. To explore the role and mechanism of eIF5 in mouse spermatogenesis, we generated Eif5 conditional knockout mice by crossing Eif5fl/fl mice with Stra8-Cre mice. The deletion of Eif5 in male germ cells caused a reduction of progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further investigations demonstrated that the deletion of Eif5 in progenitor spermatogonia led to decreased cell proliferation, increased ROS level, DNA damage and apoptosis. These observed phenotypes can be attributed to decreased protein translation efficiency in DNA repair, ubiquitination, autophagy-related genes, and increased protein translation efficiency of endoplasmic reticulum stress-related genes. These findings underscore the indispensable role of eIF5 in the proliferation and differentiation of mouse progenitor spermatogonia.

ORGANISM(S): Mus musculus

PROVIDER: GSE290869 | GEO | 2025/06/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Male germ cells-specific deletion of eukaryotic translation initiation factor 5 causes apoptosis of mouse progenitor spermatogonia by DNA repair defects and sustained endoplasmic reticulum stress

Project description:Eukaryotic translation initiation factor 5 (eIF5) promotes protein translation by regulating the ternary complex (TC) of eIF2•GTP•Met-tRNAi. A previous study showed that eIF5 is closely associated with testicular germ cell tumors (TGCTs). However, the role of eIF5 in mouse spermatogenesis remains unclear. Our study found that eIF5 is highly expressed in the cytoplasm of germ cells compared to other cells in the mouse testis. To explore the role and mechanism of eIF5 in mouse spermatogenesis, we generated Eif5 conditional knockout mice by crossing Eif5fl/fl mice with Stra8-Cre mice. The deletion of Eif5 in male germ cells caused a reduction of progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further investigations demonstrated that the deletion of Eif5 in progenitor spermatogonia led to decreased cell proliferation, increased ROS level, DNA damage and apoptosis. These observed phenotypes can be attributed to decreased protein translation efficiency in DNA repair, ubiquitination, autophagy-related genes, and increased protein translation efficiency of endoplasmic reticulum stress-related genes. These findings underscore the indispensable role of eIF5 in the proliferation and differentiation of mouse progenitor spermatogonia.

2025-06-01 | GSE290783 | GEO

SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing

Project description:Alternative splicing expands the proteome complexity and plays essential roles in tissue development and human diseases. However, how spermatogenesis is regulated by alternative splicing remains largely unknown. Here, using germ cell-specific knockout mouse model, we demonstrate that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. Depletion of Srsf10 in germ cells had little effect on the formation of SSCs but impeded the expansion of progenitor spermatogonia, leading to the failure of spermatogonia differentiation and meiosis initiation. This was evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Furthermore, the expression of genes involved in cell cycle was abnormal in all subtypes of spermatogonia identified in single-cell RNA-seq data. Notably, using isolated spermatogonia, we found that Srsf10 depletion disturbed the alternative splicing of hundreds of genes, which were preferentially associated with cell cycle, mitotic cell cycle checkpoint and germ cell development, including Dazl, Kit, Ret, Sycp1, Nasp and Bora. These data suggest that SRSF10 is critical for the expansion of progenitor spermatogonia by regulating alternative splicing, expanding our understanding of the novel mechanism underlying spermatogenesis.

2022-11-07 | GSE190646 | GEO

Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis

Project description:Spermatogenesis is precisely controlled at the transcriptional, posttranscriptional, and translational levels. Here we report that N6-methyladenosine (m6A), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive m6A mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids. Germ cell-specific inactiva- tion of the m6A RNA methyltransferase Mettl3 or Mettl14 with Vasa-Cre causes loss of m6A and depletion of SSCs. m6A depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation. Com- bined deletion of Mettl3 and Mettl14 in advanced germ cells with Stra8-GFPCre disrupts spermiogenesis, whereas mice with single deletion of either Mettl3 or Mettl14 in advanced germ cells show normal spermatogenesis. The sper- matids from double-mutant mice exhibit impaired translation of haploid-specific genes that are essential for spermio- genesis. This study highlights crucial roles of mRNA m6A modification in germline development, potentially ensuring coordinated translation at different stages of spermatogenesis.

2020-11-11 | GSE161059 | GEO

DCAF2 regulates the proliferation and differentiation of mouse progenitor spermatogonia by targeting p21 and thymine DNA glycosylase

Project description:DDB1-cullin-4-associated factor-2 (DCAF2, also known as DTL or CDT2), a conserved substrate recognition protein of Cullin-RING E3 ligase 4 (CRL4), recognises and degrades several substrate proteins during the S phase to maintain cell cycle progression and genome stability. Our study found that Dcaf2 was highly expressed in the germ cells of human and mouse testes. To determine whether DCAF2 plays a crucial role in spermatogenesis, we generated germ cell conditional Dcaf2 knockout mice by crossing Dcaf2fl/fl mice with Stra8-Cre mice. The depletion of Dcaf2 in germ cells causes a reduction in progenitor spermatogonia and differentiating spermatogonia, eventually leading to the failure of meiosis initiation and male infertility. Further study showed that depletion of Dcaf2 in germ cells caused abnormal accumulation of the substrate proteins cyclin-dependent kinase inhibitor 1A (p21) and thymine DNA glycosylase (TDG). Overexpression of p21 or TDG attenuates proliferation and increases DNA damage and apoptosis in GC-1 cells. Co-overexpression of p21 and TDG exacerbates DNA damage and apoptosis. These results suggest that DCAF2 maintains the expansion and differentiation of progenitor spermatogonia by targeting the substrate proteins p21 and TDG.

2024-05-01 | GSE259242 | GEO

Proteomic analysis of the effects of DDX20 deletion in spermatogonia

Project description:To investigate the role of DDX20 in spermatogenesis, we generated Ddx20 flox/flox Ddx4-Cre mice to make a germ cell-specific Ddx20 knockout, and isolated spermatogonia from four-day-old mouse testes by THY1 magnetic beads. We then performed proteomic analysis using protein lysates obtained from THY1 + spermatogonia.

2024-04-24 | PXD038170 |

The histone demethylase KDM1A is essential for the maintenance and differentiation of spermatogonial stem cells and progenitors

Project description:Little is known of the fundamental processes governed by epigenetic mechanisms in the supplier cells of spermatogenesis, the spermatogonial stem cells (SSCs). The histone H3 lysine demethylase KDM1A is expressed in spermatogonia. We hypothesized that KDM1A serves in transcriptional regulation of SSCs and fertility. Using a conditional deletion of Kdm1a [conditional knockout (cKO)] in mouse spermatogonia, we determined that Kdm1a is essential for spermatogenesis as adult cKO males completely lack germ cells. Analysis of postnatal testis development revealed that undifferentiated and differentiating spermatogonial populations form in Kdm1a-cKO animals, yet the majority fail to enter meiosis. Loss of germ cells in the cKO was rapid with none remaining by postnatal day (PND) 21. To gain insight into the mechanistic implications of Kdm1a ablation, we isolated PND 6 spermatogonia enriched for SSCs and analyzed their transcriptome by RNA sequencing. Loss of Kdm1a was associated with altered transcription of 1206 genes. Importantly, differentially expressed genes between control and Kdm1a-cKO animals included those that are essential for SSC and progenitor maintenance and spermatogonial differentiation. The complete loss of fertility and failure to establish spermatogenesis indicate that Kdm1a is a master controller of gene transcription in spermatogonia and is required for SSC and progenitor maintenance and differentiation.

2019-02-16 | GSE126607 | GEO

Oocyte-specific deletion of Eif5 causes apoptosis of mouse oocytes within the early growing follicles by mitochondrial fission defect and DNA damage

Project description:Mutations in several translation initiation factors are closely associated with premature ovarian insufficiency (POI). Here, we demonstrate that the conditional knockout of eukaryotic translation initiation factor 5 (Eif5) in both mouse primordial and growing oocytes resulted in the apoptosis of oocytes within the early growing follicles. The further studies revealed that Eif5 deletion in oocytes downregulated the levels of mitochondrial fission-related proteins (FIS1, MFF, MTFR2 and p-DRP1) and upregulated the levels of the integrated stress response (ISR)-related proteins (SLC7A1, SHMT2 and AARS1) and genes (Atf4, Ddit3 and Fgf21). Consistent with this, Eif5 deletion in oocytes resulted in mitochondrial dysfunction characterized by elongated form, aggregated distribution beneath the oocyte membrane, decreased ATP content and mtDNA copy number, and excessive accumulation of reactive oxygen species (ROS) and mitochondrial superoxide. Meanwhile, Eif5 deletion in oocytes led to a significant increase in the levels of DNAdamageresponse proteins (γH2AX, p-CHK2, and p53) and proapoptotic proteins (PUMA and BAX), as well as a significant decrease in the levels of anti-apoptotic protein BCL-xL. Collectively, these findings indicate that Eif5 deletion in mouse oocytes results in the apoptosis of oocytes within the early growing follicles via mitochondrial fission defect and excessive ROS-induced DNA damage. This study provides new insights into pathogenesis and genetic diagnosis for POI.

2024-08-15 | GSE263785 | GEO

BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis and male fertility

Project description:BCAS2 (Breast cancer amplified sequence 2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.

2016-11-15 | GSE89801 | GEO

Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide

Project description:The goal of this study is to evaluate the competition between eIF5 and 5MP in utilizing non-AUG translation initiation sites

2017-08-18 | GSE102786 | GEO

Retinoic acid dependent spermatogonial differentiation in mice

Project description:Spermatogonial differentiation is a developmental process that is essential for spermatogenesis, but the molecular and cellular changes that germ cells must undergo to transition from undifferentiated spermatogonia to differentiating spermatogonia remain largely undefined. Retinoic acid (RA) is necessary and sufficient for spermatogonial differentiation. Using the postnatal mouse testis, we examine the transcriptome changes that accompany spermatogonial differentiation. Spermatogenesis was synchronized by administration of potent and selective RA synthesis inhibitor; as a result, testes contained only undifferentiated spermatogonia. Then, the inhibitor was discontinued, and mice were given a single dose of exogenous RA to initiate spermatogonial differentiation. We measured transcriptomes in FACS-enriched germ cells either before RA administration, when the cells correspond to Aal spermatogonia (and a minor contribution of spermatogonial stem cells) or at two points after RA administration, when the cells correspond to A1 or A3 differentiating spermatogonia. The results of this study reveal the full transcriptome changes accompanying spermatogonial differentiation in the mouse.

2023-07-03 | GSE213716 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data